This project's specific aims are to compare, using a complete, within-subjects, 2X2 design, the subjective and cardiovascular effects of smoking caffeinated waterpipe tobacco with the effects of smoking waterpipe preparations containing caffeine and no nicotine, nicotine and no caffeine, or neither caffeine nor nicotine. Waterpipe tobacco smoking volunteers who also use caffeine will complete all four conditions, and outcome measures include plasma nicotine and caffeine levels, cardiovascular response, subjective effects, and smoking behavior. The primary hypothesis is that caffeinated waterpipe tobacco increases plasma nicotine and caffeine levels and produces cardiovascular and subjective effects that are greater than non-caffeinated waterpipe tobacco. More generally, this study will evaluate a novel delivery system of caffeine/nicotine (via volatilization) and will also help inform users of these products. Relevance: Despite the fact that smoking levels are their lowest over the past 20 years, morbidity and mortality associated with tobacco use are still alarmingly high. Waterpipe tobacco smoking is an alternative form of tobacco use that is becoming increasingly common in the U.S. and delivers physiologically active nicotine doses that may increase the probability of subsequent tobacco use. A majority of tobacco users self-administer another mild stimulant, caffeine, which has been shown to enhance the effects of nicotine when ingested in combination. Waterpipe tobacco smokers have a unique method to co-administer these two drugs: caffeinated waterpipe tobacco. However, there are no data regarding the combined effects of smoked nicotine and caffeine. Thus, this project addresses a growing public health issue (waterpipe tobacco smoking) while providing novel information regarding the effects of nicotine and caffeine when smoked in combination.